Radium 223 without androgen deprivation therapy (ADT) in patients (Pts) with biochemically recurrent prostate cancer (BCR) and PET findings in the bones.

180 Background: BCR pts have a rising PSA after definitive surgery or radiation, but negative CT/Tc99 scans. While ADT-based strategies are commonly used, they can be associated with life-altering toxicities and have not been shown to improve survival. Radium 223 is an alpha-emitting radiopharmaceutical that accumulates in areas of high bone turnover and has demonstrated a survival benefit in metastatic prostate cancer, but its benefits as a monotherapy in BCR without ADT have not been explored prior to this study. This strategy may be important as bone metastasis drives morbidity/mortality in prostate cancer. Methods: Eligible pts in this study (NCT04206319) have BCR following definitive therapy, testosterone (T) >100ng/dL, normal organ and marrow function, and negative CT/Tc99 imaging. Pts must have findings on a NaF or PSMA PET suspicious for metastatic bone disease not seen on Tc99. Pts are treated with Radium 223 at the approved dosing of 55 kBq/kg for 6 cycles. PSA declines were defined as 2 or more confirmed declines from an intra-study apex PSA (ISAP; Madan ASCO GU 2018). All pts have pre- and post-treatment PSMA and NaF imaging. Immune responses (primary endpoint) are to be evaluated at study completion. Results: 18 pts have enrolled with 16 currently evaluable for response, with a median age of 67 yrs (58-80) and PSA of 1.75 ng/ml (0.2-49.5). 14/16 pts had PSMA+ scans. 13/16 pts had NaF+ scans. There have been no missed cycles for toxicity and no grade >3 toxicities. Grade 2 toxicities have been rare and no Grade 1 or 2 changes in hemoglobin or platelets have occurred. 2 pts with rapid PSA doubling times came off for progression and were not evaluable for follow up imaging. Five pts (31%) had confirmed ISAP PSA declines of 14%, 21%, 24%, 33%, and 57% lasting 84, 173, 292, 246+, and 661+ days, respectively. 8/11 evaluable pts had evidence of decreased standard uptake value (SUV) on NaF PET imaging after treatment. Two pts had resolution of multiple PSMA+ bone findings, and one of them remains with negative bone findings on PET after 2+ years and with a stable PSA. Conclusions: Radium 223 in BCR is safe and associated with rare grade 1/2 toxicities. Decreases in SUV seen on most NaF scans suggest Radium 223 targeting of suspicious lesions. Substantial improvements in PSMA imaging have been observed. Delayed but confirmed PSA declines have been seen in 31% of pts. Radium 223 monotherapy may have a therapeutic activity in BCR and further studies are needed to define its potential role in PET+ BCR. Clinical trial information: NCT04206319 .